Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
  • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
  • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

• the present invention relates to a repelling agent, a bite repelling agent, and an arthropod-borne disease preventive agent. More particularly, the invention relates to a repelling agent for repelling arthropods (insects such as mosquito, mite, spider, etc.), a bite repelling agent for preventing bites by arthropods, and a preventive agent for infectious diseases borne by arthropods.
• arthropods insects such as mosquito, mite, spider, etc.
• a bite repelling agent for preventing bites by arthropods and a preventive agent for infectious diseases borne by arthropods.
• Malaria one of the arthropod-borne diseases (insect-borne diseases), is a disease caused by malaria protozoa borne by Anopheles species of mosquito.
• Patent Document 1 Japanese Patent Application “Kokai” No. 2004-269440
• the present inventors have conducted extensive studies seeking a measure to prevent the initial stage of malaria infection, namely, biting by the infected mosquito. As a result, the inventors have discovered that the approaching of mosquitoes as well as the biting by mosquitoes can be effectively prevented by applying aqueous solution of chlorine dioxide on the skin and have perfected the present invention based on this finding.
• the object of the present invention is to provide an agent capable of repelling arthropods such as mosquitoes or preventing biting by the arthropod even if it approaches, thus reducing the occurrence of infection of the microorganism.
• a repelling agent for repelling arthropods comprises chlorine dioxide as an effective component thereof.
• a repelling agent for preventing a bite by arthropods comprises chlorine dioxide as an effective component thereof.
• an agent for preventing arthropod-borne diseases comprises chlorine dioxide as an effective component thereof.
• arthropod-borne diseases having the above feature, it is possible to prevent arthropod-borne diseases such as diseases due to the protozoa or the parasite.
• the arthropod-borne disease is malaria.
• insects including, but not limited to, the mosquito species such as Anopheles, Culex, Mansonia, and Aedes mosquitoes, the fly species such as Tsetse fly, sandfly, blackfly, cleg, and deer fly, the lice species such as Pediculus humanus, the flea species, the assassin bug species, and the mite species such as Ixodes holocyclus, tsutsugamushi chigger, and argasid.
• the mosquito species such as Anopheles, Culex, Mansonia, and Aedes mosquitoes
• the fly species such as Tsetse fly, sandfly, blackfly, cleg, and deer fly
• the lice species such as Pediculus humanus
• the flea species the assassin bug species
• mite species such as Ixodes holocyclus, tsutsugamushi chigger, and argasid.
• arthropod-borne diseases in the present invention include (names in the parentheses are the principal arthropod(s)) malaria (Anopheles mosquito), filariasis (Anopheles, Culex, Mansonia, and Aedes mosquitoes), dengue (Aedes mosquito), yellow fever (Aedes mosquito), Japanese encephalitis (Culex tritaeniorhynchus mosquito), West Nile fever (Culex and Aedes mosquitoes), Leishmaniasis (sandfly), African trypanosomiasis ⁇ African sleeping sickness> (Tsetse fly), American trypanosomiasis ⁇ Chagas disease> (assassin bug), African eye worm disease (cleg), tularemia (deer fly and tick), typhus (Pediculus humanus corporis), relapsing fever (Pediculus humanus corporis and argasid), plague (fleas parasitic to rats), Lyme disease (tick), R. tsu
• Chlorine dioxide can be prepared as a liquid agent, a foaming agent, etc., with a solvent of water or the like and can be used as a spraying agent. Furthermore, in case it is used as an aqueous solution, in order to stabilize the concentration of chlorine dioxide, sodium chlorite (e.g. 1 ⁇ 20%), phosphate buffer solution (e.g. 1 ⁇ 20%) (e.g. pH4 ⁇ 7) can be added thereto. Also, in order to facilitate the wetting spreading of the liquid solution when it is to be applied to the skin, a surfactant agent (e.g. 0.1 ⁇ 5%) can be added thereto.
• sodium chlorite e.g. 1 ⁇ 20%
• phosphate buffer solution e.g. 1 ⁇ 20%
• pH4 ⁇ 7 e.g. pH4 ⁇ 7
• a surfactant agent e.g. 0.1 ⁇ 5%
• liquefied propane gas or the like may be charged into the container as a discharge promoting agent.
• formulations other than a spraying agent there can be cited formulations prepared by causing a known substrate to contain liquid of chlorine dioxide, thus being rendered into cream-like, gel-like, jelly-like, emulsion-like, paste-like or foam-like form (e.g. ointments, creams, lotions, sprays, liniments, etc.)
• the substrate used is not particularly limited as long as it is pharmaceutically acceptable. It can be e.g.
• lower alcohols such as ethanol, isopropanol, etc., triethanolamine, water, beeswax, oils such as jojoba oil, olive oil, cacao oil, sesame oil, soybean oil, avocado oil, camellia oil, peanut oil, polyoxyethylene hydrogenated castor oil, etc., mineral oils such as white petrolatum, liquid paraffin, silicone oils, volatile silicone oils, petrolatum, etc., and higher fatty acids such as lauric acid, myristic acid, stearic acid, oleic acid, etc.
• oils such as jojoba oil, olive oil, cacao oil, sesame oil, soybean oil, avocado oil, camellia oil, peanut oil, polyoxyethylene hydrogenated castor oil, etc.
• mineral oils such as white petrolatum, liquid paraffin, silicone oils, volatile silicone oils, petrolatum, etc.
• higher fatty acids such as lauric acid, myristic acid, stearic acid, oleic acid, etc.
• the usage amount thereof cannot be defined in particular, since it varies depending on the environment (temperature, humidity, etc.). However, in general, an agent containing chlorine dioxide by 0.01 ppm to 500 ppm, preferably, 0.1 ppm to 250 ppm, will be used as an appropriate amount, once or from twice to five times a day.
• the final pH of the liquid chlorine dioxide ranges preferably from 4.5 to 6.5. If the pH value deviates from this range, the storage stability may be reduced, so that there is a possibility of changes in its pharmacological activity during its storage, or the pharmacological activity may become weak after a long-term storage such as for two years. More preferred pH range of the chlorine dioxide agent of the invention is from 5.5 to 6.0.
• a liquid agent of chlorine dioxide was prepared as follows. To 250 mL of water with 2,000 ppm chlorine dioxide gas dissolved therein, 680 mL of water and 80 mL of 25% sodium chlorite solution were added and stirred together. Then, to the resultant mixture solution, sodium dihydrogen phosphate was added by an amount that renders the pH of the solution of 5.5 to 6.0, whereby there was obtained 1,000 mL of chlorine dioxide aqueous solution comprised of dissolved chlorine dioxide gas, sodium chlorite, and sodium dihydrogen phosphate.
• Plasmodium berghei or P. yoelii which are available (free of charge) from the Medical Zoology Department of Jichi Medical University (3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan). These species are ready to use in a study in a laboratory since they can be infected to mice, but have no infectivity to humans.
• P. falciparum FCR-3 strain ATCC 30932
• P. falciparum Honduras-1 strain ATCC 30935
• the culture medium will be RPMI 1640 culture medium (pH 7.4) added with 10% human serum, filter-sterilized, and then cultured under the conditions of 5% O 2 concentration, 5% CO 2 concentration, and 90% N 2 concentration, at temperature of 36.5° C.
• these species have infectivity to humans, caution should be taken against biting accident.
• a certain strict containment of experimental environment will be needed that will not allow escape of the mosquitoes therefrom.
• Anopheles stephensi mosquito is now available (free of charge) from the Medical Zoology Department of Jichi Medical University (3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan).
• Malaria infected mosquito can be obtained by causing a mouse (e.g. a Swiss Webster mouse) to be infected with malaria with the use of the above-described malaria protozoa and then causing Anopheles stephensi mosquito to suck blood from this infected mouse.
• a mouse e.g. a Swiss Webster mouse
• Anopheles stephensi mosquito to suck blood from this infected mouse.
• This experimental procedure will be readily performed by those skilled in the art. More particularly, as the basic experimental technique, one should follow the technique by Matsuoka et al., (Matsuoka, H., Yoshida, S., Hirai, M., and Ishii, A. Parasitol. Int. 51. 17-23, 2002), and Arai, et al. (Arai, M., Ishii, A. and Matsuoka, H. Am.
• red blood cells infected with malaria protozoa (2 ⁇ 10 6 ) are injected into the abdominal cavity of the mouse. After a lapse of three days, 2 ⁇ 5% of the red blood cells will be infected with the protozoa. Then, this mouse is anesthetized by intramuscular injection of 0.2 mg of xylazine and 2 g of ketamine. Subsequently, this mouse is subjected to blood suction by female mosquitoes for 30 minutes at 20° C. In this way, infected Anopheles stephensi mosquitoes will be prepared.
• mosquitoes are bred with the use of, as a food, a filter paper impregnated with 5% fructose and 0.05% p-aminobenzoic acid at 26° C. in the humidity range from 50 ⁇ 70% in a room lighted for 14 hours and un-lighted for 10 hours. In this way, mosquitoes infected with malaria will be obtained.
• the malaria infected mosquitoes have been successively bred with the use of infected mice in a laboratory of Professor Hiroyuki Matsuoka (present inventor) in an educational foundation: Jichi Medical University (3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan). These mosquitoes may be employed only for the purpose of conducting a confirmation experiment on the present invention (limited to the experiment performed within the above laboratory).
• mice Twenty four mice were anesthetized and divided into two groups. That is, 11 mice (mouse Nos. 1 ⁇ 11) of the 24 mice were used as a control group and water was sprayed over the skins thereof. The remaining thirteen mice (mouse Nos. 21 ⁇ 33) were used as a chlorine dioxide group and the chlorine dioxide aqueous solution prepared in the Formulation Example 1 was sprayed over the skins thereof. The hair on the backs of the mice were shaved by an electrical shaver for animals, and on these backs, water (control group) or the chlorine dioxide solution were sprayed respectively over an area of 3 cm diameter approximately. In doing this, care should be taken such that the test medical agent solution will be applied uniformly over the skin surface.
• each mouse was put on a transparent vessel (tube) (one mouse was put in each tube).
• Anopheles stephensi mosquitoes (introduced September, 1992 from London
• chlorine dioxide gas was generated by a conventional method and was bubbled in water, thus 150 ppm (2.2 mM) chlorine dioxide aqueous solution (not containing sodium chlorite or sodium dihydrogen phosphate) was obtained.
• 150 ppm (2.2 mM) chlorine dioxide aqueous solution not containing sodium chlorite or sodium dihydrogen phosphate
• mice the mice comparison 1 10 5 not contracted control group 2 12 6 contracted with spraying 3 12 6 contracted of water to skin 4 12 5 not contracted before biting 5 5 3 not contracted (blood suction) 6 5 3 contracted 7 6 2 contracted 8 6 4 not contracted 9 7 3 contracted 10 6 2 not contracted 11 7 3 contracted 88 in total 42 mosquitos 6 out of 11 out of 88 bit contracted malaria the mice (contraction ratio (biting ratio 54.5%) 47.7%) chlorine dioxide 21 12 2 contracted group with 22 12 2 not contracted spraying of 23 12 0 not contracted chlorine dioxide 24 12 2 not contracted aqueous solution 25 5 0 not contracted to skin before 26 5 0 not contracted biting (blood 27 6 0 not contracted suction) 28 6 0 not contracted 29 4 0 not contracted 30 6 0 not contracted 31 7 0 not contracted 32 7 0 not contracted 33 7 0 not contracted 101 in total 6 out of 101 1 out of 13 mosquitos contracted malaria

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• Life Sciences & Earth Sciences (AREA)
• Dentistry (AREA)
• General Health & Medical Sciences (AREA)
• Inorganic Chemistry (AREA)
• Pest Control & Pesticides (AREA)
• Plant Pathology (AREA)
• Health & Medical Sciences (AREA)
• Agronomy & Crop Science (AREA)
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• Engineering & Computer Science (AREA)
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• Agricultural Chemicals And Associated Chemicals (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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• 2009
  • 2009-05-26 TW TW104131465A patent/TWI607705B/zh active
  • 2009-05-26 WO PCT/JP2009/059609 patent/WO2009145191A1/fr active Application Filing
  • 2009-05-26 US US12/994,458 patent/US20110183004A1/en not_active Abandoned
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